Highlights From the Latest in Diabetes Research

Type 1 diabetes (T1D) is a complex disease whose pathogenesis involves islet-specifi c autoreactive T cells that destroy insulin producing β-cells in the pancreas. Autoreactive T cells are usually under tight regulation, and exactly how these cells overcome the inhibition that leads to disease is not well understood. Recent studies have focused on the actions of interleukin (IL)-7, a crucial cytokine for T-cell homeostasis that may also have a role in reversing suppressor functions in T cells, thus promoting T1D. Recently, two laboratories examined IL-7’s actions through the IL-7 receptor-α (IL-7Rα) in T1D using IL-7Rα antibodies in NOD mice. Both groups demonstrated prevention and reversal of T1D in NOD mice by IL-7Rα blockade. IL-7Rα blockade upregulated expression of the negative regulator programmed death 1 (PD-1) on the cell surface of CD4 and CD8 T effector and memory cells in the pancreas. PD-1 and its ligand PD-1L are tightly correlated with maintaining tolerance of effector T cells in infl amed tissues and protecting against autoimmune diabetes. Previous studies have correlated loss of PD-1 in knockout NOD mice with increases in IFN-γ production and progression to diabetes. Both groups demonstrated that even with blockade of the IL-7Rα, use of an anti–PD-1 antibody led to diabetic relapse, providing evidence for a role of PD-1 in the therapeutic effects of IL-7Rα blockade.